Ohba_2002_J.Submicrosc.Cytol.Pathol_34_367

This study was aimed to demonstrate the regeneration of skeletal muscle fibers in the stroma reaction during tumor invasion, using the rat model of tongue carcinoma. By oral administration of 4-nitroquinoline N-oxide, squamous cell carcinoma (SCC) appeared in the epithelium, and deeply invaded the muscular layer, inducing the stroma reaction around the tumor. Regenerating muscle fibers, characterized by the immature profiles of sparse myofibrils, centrally disposed multi-nuclei, and abundant mitochondria, were extended from the surrounding normal muscles into the stroma. By immunohistochemistry, some of them expressed BF-45, a marker for an early stage of myodifferentiation, similar to the regenerating muscle fibers in the bupivacaine hydrochloride-induced injury. They were closely associated with the stromal components such as ED-1-positive macrophages, alpha-smooth muscle actin-positive myofibroblasts, and factor VIII-related antigen-positive vascular endothelial cells, suggesting the roles of their interactions in muscle regeneration. Immature muscle fibers were usually devoid of acetylcholinesterase-positive endplates on them, but some were reinnervated by the terminal axons. The present results indicate that skeletal muscle regeneration is induced in association with the stroma reaction during SCC invasion in the tongue.